Effects of pure tocotrienols on the status of endothelial activation, inflammation, oxidative stress and plaque stability in the prevention of early and established experimental atherosclerosis / Nurmazni Zulkafli

Atherosclerosis is one of the leading causes of coronary artery disease (CAD). Studies on the cardioprotective activities of tocotrienols (T3) in the absence of alpha tocopherol (TCP) remain obscure. The aim of this study was to evaluate the effects of pure T3 supplementation on lipid lowering, tissue endothelial activation and inflammatory biomarkers, and oxidative stress in early and established atherosclerosis rabbit model. Fifteen New Zealand white rabbits were divided into two intervention groups: Al [given 2 months normal diet (ND) and 2 weeks high cholesterol diet (HCD)] and A2 (given 2 months ND and 2 months HCD). Each group was further divided into three groups: T3- 4mg/kg and T3-15mg/kg supplementation groups given pure T3 (delta90%-gammal0%) and placebo. Interventions were given throughout the study. Fasting serum lipids, plasma C-reactive protein and 8-isoprostanes were measured at baseline, 4, 8, 10, 12, 16 weeks

Atheroprotective effects of pure tocotrienol supplementation in the treatment of rabbits with experimentally induced early and established atherosclerosis

Background: Atherosclerosis is the main cause of coronary artery disease -related deaths worldwide. The atheroprotective properties of pure tocotrienols (T3) in the absence of alpha-tocopherol (α-TCP) in vitamin E has not been extensively examined. Aim: To determine the atheroprotective properties of T3 in early and established atherosclerosis rabbits. Methods: Thirty New Zealand white rabbits were divided into two groups, B1 and B2 which represent early [fed 1% high cholesterol diet (HCD) for 2 weeks] and established (fed 1% HCD for 8 weeks) atherosclerosis. Each group was subdivided into three intervention arms: 1) T3–4 mg/kg, 2) T3–15 mg/kg and 3) vehicle without T3 (T3 negative) for 8 weeks. Serial fasting blood samples were obtained for lipid profile, and whole lengths of aorta were used to determine tissue markers of endothelial activation, inflammation and plaque stability. Results: In B1, atherosclerotic lesion in T3–4 mg/kg group was significantly reduced (p=0.008), while aortic tissue expression of vascular cellular adhesion molecule 1 (VCAM-1), interleukin-6 (IL-6) and matrix metalloproteinase (MMP-12) was reduced in T3–4 mg/kg compared to T3-negative rabbits group (0.2±0.1 vs. 28.5±3.1%; 3.0±1.6 vs. 14.0±1.7%; and 5.2±2.2 vs. 27.7±0.8%, respectively, p<0.05). T3–15 mg/kg group showed reduction in VCAM-1, E-selectin, IL-6 and MMP-12 (3.9±1.9 vs. 28.5±3.1%; 10.3±0.5 vs. 59.8±8.5%; 2.6±1.7 vs. 14.0±1.7%; and 16.2±3.2 vs. 27.7 0.8%, respectively, p<0.05). In B2, T3–4 mg/kg group reduced aortic tissue expression of intercellular adhesion molecule 1 (ICAM-1), E-selectin, IL-6, MMP-12 and MMP-9 compared to T3-negative rabbits group (29.9±2.4 vs. 55.3±1.3%; 26.7±1.5 vs. 60.5±7.6%; 15.7±0.7 vs. 27.7±4.8%; 34.8±2.7 vs. 46.5±3.4%; and 25.89±3.9 vs. 45.9±1.7%, respectively, p<0.05). T3–15 mg/kg group showed reduced VCAM-1, ICAM-1, E-selectin, IL-6, MMP-12 and MMP-9 (20.5±3.3 vs. 35.6±2.5%; 24.9±1.3 vs. 55.3±1.3%; 29.9±6.7 vs. 60.5±7.6; 11.3±2.2 vs. 27.7±4.8%; 23.0±1.7 vs. 46.5±3.4%; and 17.6±1.9 vs. 45.9±1.7%, respectively, p<0.05. Conclusion: These findings suggest the possible atheroprotective role T3 plays as an adjunct supplementation to standard treatment in the prevention of CAD